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Rôle du facteur pro-angiogène EG-VEGF dans le développement placentaire au cours de premier trimestre de grossesse

Abstract : Placental development is a process that is finely controlled. It is characterized by early and deep invasion of the endometrium and the first third of the myometrium by extravillous cytotrophoblasts that participate to the remodeling of the spiral arteries and to the establishment of the feto-maternal circulation. Poor remodeling of spiral arteries by trophoblastic cells, leads to the development pregnancy pathologies such as, Preeclampsia (PE) and Intra-Uterine Growth Restriction (IUGR). During the last decade, our team has gathered interesting data that propose the new factor, EG-VEGF (Endocrine Gland Derived Vascular Endothelial Growth Factor) as a potential marker for PE. My thesis project aimed at further characterizing the role of EG-VEGF during pregnancy. Three main axis were addressed, i) The study of the regulation of EG-VEGF by PPARγ (Peroxisome proliferator-activated receptor gamma), ii) The study of the role in hematopoietic and angiogenic placental cells differentiations and iii) The development of an in vivo model of PE. My thesis showed that 1) EG-VEGF and PROKR2 expression are upregulated by PPARγ, 2) that the regulation of intra-placental vascularization and trophoblastic invasion by PPARγ is mediated by EG-VEGF through PROKR1 and PROKR2 and through PROKR2 receptors, respectively, 3) that EG-VEGF controls hematopoietic and endothelial cell differentiation and 4) that maintenance of EG-VEGF production beyond its normal period of secretion during pregnancy leads to the development of PE in a gravid mouse model. Altogether, these projects contributed to have a better knowledge about physiological mechanisms of placental development and about a key factor of placentation EG-VEGF. Moreover they improved our understanding of the origins of pregnancy diseases establishment such as PE and RCIU.
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Vanessa Garnier. Rôle du facteur pro-angiogène EG-VEGF dans le développement placentaire au cours de premier trimestre de grossesse. Biologie cellulaire. Université de Grenoble, 2014. Français. ⟨NNT : 2014GRENV021⟩. ⟨tel-01553460⟩

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